This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.